In assisted reproductive technology (ART), pregnancy and birth rates following in vitro fertilization (IVF) attempts remain low. Indeed, 2 out of 3 IVF cycles fail to result in pregnancy (SART 2004) and more than 8 out of 10 transferred embryos fail to implant (Kovalevsky and Patrizio, 2005). In addition, more than 50% of IVF-born babies are from multiple gestations (Reddy et al., 2007). Preterm deliveries that result from multiple pregnancies caused by ART are estimated to account for approximately $890 million of U.S. health care costs annually (Bromer and Seli, 2008).
Subjective morphological parameters are still a primary criterion to select healthy embryos used for in IVF and ICSI programs. However, such criteria do not truly predict the competence of an embryo. Many studies have shown that a combination of several different morphologic criteria leads to more accurate embryo selection (Balaban and Urman, 2006; La Sala et al., 2008; Scott et al., 2000). Morphological criteria for embryo selection are assessed on the day of transfer, and are principally based on early embryonic cleavage (25-27 h post insemination), the number and size of blastomeres on day two or day three, fragmentation percentage and the presence of multi-nucleation in the 4 or 8 cell stage (Fenwick et al., 2002).
However, a recent study has shown that the selection of oocytes for insemination does not improve outcome of ART as compared to the transfer of all available embryos, irrespective of their quality (La Sala et al., 2008). There is a need to identify viable embryos with the highest implantation potential to increase IVF success rates, reduce the number of embryos for fresh replacement and lower multiple pregnancy rates.
For all these reasons, several biomarkers for embryo selection are currently being investigated (Haouzi et al., 2008; Pearson, 2006). As embryos that result in pregnancy differ in their metabolomic profiles compared to embryos that do not, some studies are trying to identify a molecular signature that can be detected by non-invasive evaluation of the embryo culture medium (Brison et al., 2004; Gardner et al., 2001; Sakkas and Gardner, 2005; Seli et al., 2007; Zhu et al., 2007).
Genomics are also providing vital knowledge of genetic and cellular function during embryonic development. (McKenzie et al., 2004) and (Feuerstein et al., 2007) have reported, that the expression of several genes in cumulus cells, such as cyclooxygenase 2 (COX2), was indicative of oocyte and embryo quality. Gremlin 1 (GREM1), hyaluronic acid synthase 2 (HAS2), steroidogenic acute regulatory protein (STAR), stearoyl-coenzyme A desaturase 1 and 5 (SCD1 and 5), amphiregulin (AREG) and pentraxin 3 (PTX3) have also been shown to be positively correlated with embryo quality (Zhang et al., 2005). More recently, the expression of glutathione peroxidase 3 (GPX3), chemokine receptor 4 (CXCR4), cyclin D2 (CCND2) and catenin delta 1 (CTNND1) in human cumulus cells have been shown to be inversely correlated with embryo quality, based on early-cleavage rates during embryonic development (van Montfoort et al., 2008). But, despite the fact that early cleavage has been shown to be a reliable biomarker for predicting pregnancy (Lundin et al., 2001; Van Montfoort et al., 2004; Yang et al., 2007), gene expression profiles of cumulus cells had not been studied with respect to pregnancy outcome.